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Review ArticleReview Article

Anti-Inflammatory Effects of Omega-3 Fatty Acids in the Brain: Physiological Mechanisms and Relevance to Pharmacology

Sophie Layé, Agnès Nadjar, Corinne Joffre and Richard P. Bazinet
Robert Dantzer, ASSOCIATE EDITOR
Pharmacological Reviews January 2018, 70 (1) 12-38; DOI: https://doi.org/10.1124/pr.117.014092
Sophie Layé
Institut National pour la Recherche Agronomique and Bordeaux University, Nutrition et Neurobiologie Intégrée, UMR 1286, Bordeaux, France (S.L., A.N., C.J.); and Department of Nutritional Sciences, University of Toronto, Ontario, Canada (R.P.B.)
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Agnès Nadjar
Institut National pour la Recherche Agronomique and Bordeaux University, Nutrition et Neurobiologie Intégrée, UMR 1286, Bordeaux, France (S.L., A.N., C.J.); and Department of Nutritional Sciences, University of Toronto, Ontario, Canada (R.P.B.)
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Corinne Joffre
Institut National pour la Recherche Agronomique and Bordeaux University, Nutrition et Neurobiologie Intégrée, UMR 1286, Bordeaux, France (S.L., A.N., C.J.); and Department of Nutritional Sciences, University of Toronto, Ontario, Canada (R.P.B.)
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Richard P. Bazinet
Institut National pour la Recherche Agronomique and Bordeaux University, Nutrition et Neurobiologie Intégrée, UMR 1286, Bordeaux, France (S.L., A.N., C.J.); and Department of Nutritional Sciences, University of Toronto, Ontario, Canada (R.P.B.)
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Robert Dantzer
Roles: ASSOCIATE EDITOR
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Abstract

Classically, polyunsaturated fatty acids (PUFA) were largely thought to be relatively inert structural components of brain, largely important for the formation of cellular membranes. Over the past 10 years, a host of bioactive lipid mediators that are enzymatically derived from arachidonic acid, the main n-6 PUFA, and docosahexaenoic acid, the main n-3 PUFA in the brain, known to regulate peripheral immune function, have been detected in the brain and shown to regulate microglia activation. Recent advances have focused on how PUFA regulate the molecular signaling of microglia, especially in the context of neuroinflammation and behavior. Several active drugs regulate brain lipid signaling and provide proof of concept for targeting the brain. Because brain lipid metabolism relies on a complex integration of diet, peripheral metabolism, including the liver and blood, which supply the brain with PUFAs that can be altered by genetics, sex, and aging, there are many pathways that can be disrupted, leading to altered brain lipid homeostasis. Brain lipid signaling pathways are altered in neurologic disorders and may be viable targets for the development of novel therapeutics. In this study, we discuss in particular how n-3 PUFAs and their metabolites regulate microglia phenotype and function to exert their anti-inflammatory and proresolving activities in the brain.

Footnotes

    • Received April 30, 2017.
    • Accepted September 5, 2017.
  • S.L., C.J., and A.N. are supported by Institut National pour la Recherche Agronomique, Bordeaux University, Foundation for Medical Research (DRM.20101220441), and the French Foundation (FDF, #00070700). R.P.B. is supported by the Canadian Institutes of Health Research and the Natural Sciences and Engineering Council of Canada, and holds the Canada Research Chair in Brain Lipid Metabolism.

  • https://doi.org/10.1124/pr.117.014092.

  • Copyright © 2017 by The American Society for Pharmacology and Experimental Therapeutics
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Pharmacological Reviews: 70 (1)
Pharmacological Reviews
Vol. 70, Issue 1
1 Jan 2018
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Review ArticleReview Article

New Insights into the Impact of Omega-3 in Microglia

Sophie Layé, Agnès Nadjar, Corinne Joffre and Richard P. Bazinet
Pharmacological Reviews January 1, 2018, 70 (1) 12-38; DOI: https://doi.org/10.1124/pr.117.014092

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Review ArticleReview Article

New Insights into the Impact of Omega-3 in Microglia

Sophie Layé, Agnès Nadjar, Corinne Joffre and Richard P. Bazinet
Pharmacological Reviews January 1, 2018, 70 (1) 12-38; DOI: https://doi.org/10.1124/pr.117.014092
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  • Article
    • Abstract
    • I. Introduction
    • II. Definition of PUFAs
    • III. Mechanisms of Entry of PUFAs into the Brain
    • IV. Anti-Inflammatory Activities of n-3 PUFAs in the Brain
    • V. Microglia as a Target for n-3 PUFAs and SPMs
    • VI. Pharmacological Considerations on the Use of LC-PUFAs or SPMs as Effective Anti-Inflammatory Drugs in the Brain—Clinical Use
    • VII. Conclusion
    • Authorship Contributions
    • Footnotes
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